The angiotensin converting enzyme inhibitor captopril, which has remarkable antihypertensive activity and has the structure ##STR2## may be prepared by reacting the resolved D-(-)-3-acetylthio-2-propanoic acid with thionyl chloride to form its acid chloride, reacting the acid chloride with L-proline in the presence of base and then deacylating the resulting proline derivative to give captopril.
The starting D-(-)-3-acetylthio-2-propanoic acid may be obtained by resolution of DL-3-acetylthio-2-methylpropanoic acid employing an optically active amine. For example, U.S. Pat. No. 4,297,282 to Ohashi (assigned to Sumitomo Chemical Company) discloses a process for the optical resolution of DL-.alpha.-methyl-.beta.-acylthiopropionic acids to ultimately obtain D-.alpha.-methyl- .beta.-acylthiopropionic acid (useful in preparing captopril) wherein the resolving agent employed is an optically active amine of the formula ##STR3## wherein R.sub.1 is methyl and R.sub.2 is .alpha.-naphthyl or R.sub.1 is ##STR4## Y are each halogen, methyl or halogen. Thus, such optically active amines include ##STR5##
U.S. Pat. No. 4,325,886 to Ohashi (assigned to Sumitomo Chemical Company) is similar in disclosure to U.S. Pat. No. 4,297,282 except that the optically active amine employed has the formula ##STR6## wherein R.sub.2 is methyl, isopropyl or isobutyl.
U.S. Pat. No. 4,346,045 to DeHeij (assigned to Oce-Andeno B.V.) discloses a process for resolving DL-S-benzoyl-.beta.-mercaptoisobutyric acid using D-(+)-N-benzyl-.alpha.-phenethylamine (NBPA), that is, ##STR7##